This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The long-term goal of this research is to determine mechanisms of metastasis and immune escape in epithelial ovarian cancer. The cells of this cancer type express a very large protein called MUC16. MUC16 is a large, heavily glycosylated protein whose molecular weight is estimated at over 3 million Da. We have shown previously that MUC16 aids ovarian cancer cells in spreading throughout the peritoneal cavity by attaching specifically to another protein called mesothelin. Mesothelin is expressed by mesothelial cells that line the peritoneal cavity as well as the organs within the peritoneal cavity[unreadable]both of which are common sites of ovarian cancer metastasis. MUC16 also contributes to ovarian cancer immune evasion. Natural killer (NK) cells require close contact (called immune synapses) with a target cell to be able to lyse it. This close contact allows the NK cells to polarize molecules that are destructive to the target cell at the NK/target cell interface. When the large and anti-adhesive protein MUC16 is expressed on the tumor cell surface, NK cells are prevented from forming immune synapses and destroying the tumor cell. This research on the both the metastatic and immune evasive roles of MUC16 may lead us to new therapies for epithelial ovarian cancer.